SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors.
Signal Transduct Target Ther
; 9(1): 96, 2024 Apr 24.
Article
de En
| MEDLINE
| ID: mdl-38653754
ABSTRACT
The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP. SOX9 promotes the nuclear translocation of YAP by direct interaction. Importantly, we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP. Additionally, we have discovered a novel asymmetrical dimethylation of YAP at Arg-124 (YAP-R124me2a) catalyzed by PRMT1. YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers. Furthermore, we disrupted the interaction between SOX9 and YAP using a competitive peptide, S-A1, which mimics an α-helix of SOX9 containing Asp-125. S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth. This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Facteurs de transcription
/
Noyau de la cellule
/
Protéines adaptatrices de la transduction du signal
/
Facteur de transcription SOX-9
/
Protéines de signalisation YAP
Limites:
Animals
/
Humans
Langue:
En
Journal:
Signal Transduct Target Ther
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine